Recent studies form animal models have rekindled interest in the role of the hypothalamic-pituitary-adrenal (HPA) axis and other neuroendocrine factors in rheumatoid arthritis (RA) and related autoimmune diseases. The pituitary-adrenal system was evaluated in 8 female patients with active RA treated with long-term low dose corticosteroids and were compared with 16 female age-matched controls. Data were obtained demonstrating elevated but submaximal ACTH and cortisol production in the patients with RA. The data are consistent with, but do not prove, the hypothesis that some rheumatoid arthritis patients may have inappropriately blunted HPA axis responses to inflammation.